Unknown

Dataset Information

0

P85? recruitment by the CD300f phosphatidylserine receptor mediates apoptotic cell clearance required for autoimmunity suppression.


ABSTRACT: Apoptotic cell (AC) clearance is essential for immune homeostasis. Here we show that mouse CD300f (CLM-1) recognizes outer membrane-exposed phosphatidylserine, and regulates the phagocytosis of ACs. CD300f accumulates in phagocytic cups at AC contact sites. Phosphorylation within CD300f cytoplasmic tail tyrosine-based motifs initiates signals that positively or negatively regulate AC phagocytosis. Y276 phosphorylation is necessary for enhanced CD300f-mediated phagocytosis through the recruitment of the p85? regulatory subunit of phosphatidylinositol-3-kinase (PI3K). CD300f-PI3K association leads to activation of downstream Rac/Cdc42 GTPase and mediates changes of F-actin that drive AC engulfment. Importantly, primary macrophages from CD300f-deficient mice have impaired phagocytosis of ACs. The biological consequence of CD300f deficiency is predisposition to autoimmune disease development, as Fc?RIIB-deficient mice develop a systemic lupus erythematosus-like disease at a markedly accelerated rate if CD300f is absent. In this report we identify the mechanism and role of CD300f in AC phagocytosis and maintenance of immune homeostasis.

SUBMITTER: Tian L 

PROVIDER: S-EPMC4151829 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

altmetric image

Publications

p85α recruitment by the CD300f phosphatidylserine receptor mediates apoptotic cell clearance required for autoimmunity suppression.

Tian Linjie L   Choi Seung-Chul SC   Murakami Yousuke Y   Allen Joselyn J   Morse Herbert C HC   Qi Chen-Feng CF   Krzewski Konrad K   Coligan John E JE  

Nature communications 20140101


Apoptotic cell (AC) clearance is essential for immune homeostasis. Here we show that mouse CD300f (CLM-1) recognizes outer membrane-exposed phosphatidylserine, and regulates the phagocytosis of ACs. CD300f accumulates in phagocytic cups at AC contact sites. Phosphorylation within CD300f cytoplasmic tail tyrosine-based motifs initiates signals that positively or negatively regulate AC phagocytosis. Y276 phosphorylation is necessary for enhanced CD300f-mediated phagocytosis through the recruitment  ...[more]

Similar Datasets

| S-EPMC3752698 | biostudies-literature
| S-EPMC8213124 | biostudies-literature
| S-EPMC1866200 | biostudies-other
| S-EPMC1383669 | biostudies-literature
| S-EPMC3077249 | biostudies-literature
| S-EPMC5487349 | biostudies-literature
| S-EPMC6920856 | biostudies-literature
| S-EPMC4306451 | biostudies-literature
| S-EPMC2651016 | biostudies-literature
| S-EPMC8143223 | biostudies-literature